Through the studies proposed in this project we hope to: a) help provide a more comprehensive understanding of how the acinar cell of the pancreas secretes its particular mixture of proteins, the digestive enzymes; b) test the hypothesis that these protein molecules can cross specialized biological membranes by passing through them; c) gain a better understanding of the internal organization of the secretion granule of the pancreas, the zymogen granule, and how its organization relates to the secretion process; d) learn about the nature and potential biological significance of the enteropancreatic circulation of digestive enzyme; and e) extend our study of ion transport in the pancreas by focusing upon the relationship between the transport of ions across the acinar cell and the secretion of digestive enzyme. We will attempt to achieve these goals using a variety of experimental approaches and techniques drawn from physiology, biophysics, biochemistry, and cell biology.